Obesity is a condition in which excess energy has accumulated as a fat in the body as a result of energy intake being greater than energy expenditure. According to the 2005 Korea National Health and Nutrition Examination Survey, the prevalence of obesity among Korean adults aged 20 years and older was 31.8% and it has increased by more than double from 14.8% in 1995 during the past 10 years (Ministry of Health & Welfare. 2006. The third Korea National Health and Nutrition Examination Survey). Due to this increasing tendency, the socioeconomic loss caused by obesity has increased annually from 1,700 billion won in 2001 and the government has set a main objective to maintain the prevalence of adult obesity of around 30% by 2010 in Health Plan (Ministry of Health & Welfare. 2005. Health Plan. pp. 61-64). Since obesity not only has its own problems, but it can also cause diseases such as cardiovascular diseases, diabetes, respiratory diseases, or osteoarthritis, much attention has been focused on obesity from around the world (Antipatis V. J. et al., 2001, Obesity as a global problem. In International textbook of obesity. Per Bjorntorp, ed. John Wiley & Sons Ltd, Chichester, UK. pp. 3-22) and World Health Organization deals with obesity as a global nutritional problem and recognizes it as a disease that should be treated, not a simple risk factor that damages health (World Health. 1998. Obesity: Preventing and managing the global epidemic. Report of WHO Consultation on Obesity, Geneva). Obesity is caused by a combination of excessive energy intake, lack of physical activity as well as secretory factors in the nerve system, medications, genetic factors, etc. and diet, physical exercise, behavior modification therapy, drug treatments, etc. are used for relieving obesity.
Recently, a lot of research on developing therapeutic agents for obesity has been made and one of such research is about pancreatic lipase inhibitors. Pancreatic lipase is a key enzyme which degrades triglycerides into 2-monoacylglycerol and fatty acids (Bitou N. et al., 1999, Lipid 34:441-445) and a currently known representative pancreatic lipase inhibitor is tetrahydrolipstatin (orlistat), a derivative of lipstatin derived from Streptomyces toxitricini. Orlistat (Xenical) which is now commercially available as a drug has been known to be one of the most efficient pancreatic lipase inhibitors enough to prevent the absorption of approximately 30% dietary fat (Drent M. et al., 1995, Int. J. Obesity. 19:221-226). Despite this, orlistat has been known to have side effects such as gastrointestinal problems, hypersensitivity, dyscholia, inhibition of the absorption of fat-soluble vitamins, etc. (Peter C. et al., 2001, Br. J. Clin. Pharmacol. 51:135-141). According to FDA guidelines for weight-loss treatment, anti-obesity drugs for long-term use should result in a efficacy of 5% weight loss from the weight before administration of the drugs and the weight-loss effect should be maintained for at least 12 months. However, after two years of long-term administration of orlistat, the weight loss was merely 3 to 5% compared to a diet alone and the side effect of inhibiting the absorption of fat-soluble vitamins A, D, and E was showed. Orlistat was released in 1998 and sales were $900,006,300 in 2001, however, had since slowed owing to such side effect and poor efficacy. Thus, research has recently been performed on developing pancreatic lipase inhibitors from foods and natural products which have no side effects (Yamamoto M. et al., 2000, Int. J. Obesity. 24:758-764).
Anti-obesity materials developed using natural products are classified into categories by mechanisms of action, namely those which: involve in suppressing appetite; inhibit fat digestion and absorption; induce heat generation and inhibit fat accumulation; and regulate lipid metabolism. Examples of those which involve in suppressing appetite include hydroxycitric acid (HCA), Olibra, dietary fibers such as chicory and inulin. Examples of those which inhibit fat digestion and absorption include chitosan, flavonoids, etc. Examples of those which induce heat generation and inhibit fat accumulation include capsaicin in chili peppers, catechin in green tea, retinoic acids, etc. L-carnitine, conjugated linoleic acid (CLA), calcium in milk and related proteins are reported for examples of those which regulate lipid metabolism. Examples of medicinal herbs which have effect on weight control include poncirus, Zingiber mioga, Cassia tora, green tea, pine needles, sophora, cnidium, evodia, etc. (Kim M. H., 2004, Korean J. Heath Psychol. 9:493-509, Reddy P. et al., 1998, Formulary 33:943-959, Burns A. A. et al., 2002, Eur. J. Clin. Nutr. 56:368-377, Delzenne N. M. et al., 2005, Br. J. Nutr. 1:157-161, Zacour A. C. et al, 1992, J. Nutr. Sci. Vitamilol. 38:609-613, Griffiths D. W. et al., 1986, Adv. Exp. Med. Biol. 1999:509-516). Consumers have great interests in therapeutic agents made from natural materials which have little side effects, but have excellent medicinal efficacy and accordingly, in order to meet the demand, there is need for developing safe and highly efficient natural remedies.
Meanwhile, Polygonum cuspidatum Sieb. et Zucc. (=Reynotria japonica Houtt.) is a member of the Polygonaceae family, an herbaceous perennial, having a thick rhizome and stems of approximately 1.5 m in height. Leaves are alternate, oval, about 6 to 12 cm in length, pointed at the tip, and leaves are on long petiole. Flowers are dioecism, bloom in June to August. Fruits are achene, triangular oval, and glossy dark brown. It grows in mountain valleys throughout the country and is distributed in Japan, China, and Taiwan (Bae Gihwan, Medicinal plants of Korea, Kyohak Publishing Co., Ltd., 2003, p. 89). Rhizomes and roots of Polygonum cuspidatum are called as Polygonum cuspidatum or Polygoni Rhizoma (=Reynoutriae Rhizoma) and included in the medium grade of wood section from Bencao Gangmu (Compendium of Materia Medica). In Korean folk medicine, it has been used as a palliative and diuretic and in the treatment of pyodermatitis, cystitis, cancers, etc. and in Chinese medicine, it has been used for expelling wind dampness, breaking blood stasis, treating menorrhalgia, relieving cough and relieving spasm (Yuk Changsu, Illustrated Guide to Asian Herbal Medicine, Kyungwon Publishing Co., Ltd., 1997, p. 140; Ji Okpyo, 1975, Korean Journal of Pharmacognosy, 6:1-4). Reported its medical actions include inhibition of lipid metabolism (Masaki H., et al., 1995, Biol. Pharm. Bull. 18:162-166, 1995), inhibition of protein tyrosine kinase (Jayatilake G. S., et al., 1993, J. Nat. Prod. 56: 1805-1810), inhibition of mutagenicity (Su et al., 1995, Mutat. Res. 329:205-212), etc. It has been known that its main components are stilbenes, anthraquinone, and glycosides thereof, including polydatin, resveratrol, emodin, physcion, and chrysophanoic acid (Pan et al., 2000, Zhong Yao Cai, 23: 56-58; Zhang, 1999, Tianjin Yi Yao, 11:13-14). However, research on its fractions has not yet been conducted so far and there has been no report that the fractions are effective in treating and preventing obesity.
Thus, the present inventors have tried to develop an agent for treating and preventing obesity using natural drugs and found that fractions of Polygonum Cuspidatum extracts are effective in inhibiting pancreatic lipase activity and fat absorption, thereby leading to completion of the present invention.